title: Oxidative stress decreases uptake of neutral amino acids in a human placental cell line (BeWo cells).
abstract: Increased oxidative stress (OS) is implicated in the pathophysiology of several pregnancy disorders. We aimed to investigate the effect of tert-butylhydroperoxide (TBHP)-induced OS upon the placental transport of the neutral amino acids L-methionine (L-Met) and L-alanine (L-Ala), by using a human trophoblast cell model (BeWo cells). TBHP reduced both total and Na(+)-independent (14)C-L-Met intracellular steady-state accumulation over time (Amax), by reducing non-system L-mediated uptake - most probably system y(+) - while having no effect on system L. Moreover, TBHP reduced total (14)C-L-Ala Amax through an inhibition of system A. The effect of TBHP upon total, but not system A-mediated, (14)C-L-Ala uptake was dependent upon phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) activation, and was completely prevented by the polyphenol quercetin. In conclusion, a reduction in placental uptake of neutral amino acids may contribute to the deleterious effects of pregnancy disorders associated with OS.
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal. jaraujo@med.up.pt
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Araújo
authors.forename: Ana
authors.initials: A
authors.lastname: Correia-Branco
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Pereira
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Pinho
authors.forename: Elisa
authors.initials: E
authors.lastname: Keating
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
mesh_terms: D000409:Alanine / Q000378:metabolism*; D021542:Amino Acids, Neutral / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D021542:Amino Acids, Neutral; D020122:tert-Butylhydroperoxide; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D000409:Alanine
keywords: 2-amino-2-norbornanecarboxylic acid; A(max); BCH; EGCG; LAT; MeAIB; N-ethylmaleimide; NEM; Na(+)-coupled neutral amino acid transporter; Nutrients; OS; Oxidative stress; Placenta; SNAT; STB; TBHP; Transport; accumulation at steady state; epigallocatechin-3-gallate; k(in); k(out); l-type amino acid transporter; oxidative stress; rate constant for inward transport; rate constant for outward transport; syncytiotrophoblast; tert-butylhydroperoxide; α-(methylamino)isobutyric acid